Abstract
Purpose: :
Mice have not been widely used for studying intraocular pressure (IOP) mainly due to the technical difficulty of working with this small species in this area. However, advancements in measuring mouse IOP in a high–throughput manner and gene knockout technology make this species ideal for the identification of novel genes regulating IOP. We are examining the physiology of 5,000 different lines of knockout mice representing pharmacologically tractable targets. The goals of this study were to determine if IOP in mice responds to pharmacological agents used in clinical settings (benchmarking) and to determine whether the baseline IOP in specific gene knockouts is altered.
Methods: :
C57BL/6 mice or C57BL/6.129 hybrid mice were used for IOP studies. IOP was measured in anesthetized mice by micro–needle cannulation of the anterior chamber. Effects of brimonidine, timolol, acetazolamide, latanoprost, or Y–27632 (a known rho–associated coiled–coil forming kinase (ROCK) inhibitor) on baseline IOP were measured in wild type mice. Mice deficient in rho–associated coiled–coil forming kinase 2 (ROCK2) were generated from Omnibank, a sequence–tagged gene–trap library of >270,000 mouse embryonic stem cell clones. The baseline IOP of mice lacking ROCK2 was compared to their wild type controls.
Results: :
The mean IOP of the C57BL/6.129 hybrid mice was 11.67 mm Hg (n = 1,132). Treatment of these mice with brimonidine, timolol, acetazolamide, latanoprost, or Y–27632 resulted in a significant reduction in IOP. Mice deficient in ROCK2 also exhibited an IOP decrease of 2.38 mm Hg, comparable to that observed with the pharmacological inhibitor Y–27632 (mean delta IOP = 1.6 mm Hg).
Conclusions: :
Pharmacological benchmarking demonstrates that wild type mice respond to known ocular hypotensive agents and are an ideal model for studying mechanisms regulating IOP. This suggests that mice with specific gene deletions can be used to identify novel therapeutic targets for treating ocular hypertension.
Keywords: transgenics/knock-outs • outflow: trabecular meshwork • inflow/ciliary body